tbuckley/cabot-search huggingface dataset:
Inpatient complications of immunotherapy-associated colitis in solid malignancies: Real-world data analysis.
Authors: Rayli Pichardo, Yazan Abu Omar, Ding Wang
Journal: Journal of Clinical Oncology (2022)

2657 Background: Immune checkpoint inhibitors (ICPis) and their containing regimens have been proven beneficial for the treatment of multiple malignancies, while immune-related adverse events (IrAEs) have become constant safety challenges in their clinical management through all ICPi therapies. Diarrhea resulted from immune-mediated colitis has been one of the most common IrAEs. The Aim of this study is to evaluate the real-world incidence and factors that contributed to colitis among patients hospitalized for anti-neoplastic immunotherapy using a large nation-wide database. Methods: We performed a retrospective analysis with the National Inpatient Sample (NIS) using ICD10-CM and PCS codes to identify patients with solid tumors hospitalized for immunotherapy between October 2015 and 2018. A comparison analysis was made between patients who developed diarrhea (or colitis) or not during their hospitalizations. Patient characteristics included past medical history, location, charges, length of stay (LOS) and inpatient complications variables, data were compared between the two groups. Results: The data from 5,795 admissions for immunotherapy were included, of which 615 (10.61%) inpatient events were complicated by diarrhea (colitis). Patients with diarrhea tended to be males (60%), slightly older at age 57 years, higher percentage of white patients (78%) though not statistically significant from those who did not have colitis. On the other hand, the length of inpatient stay was statistically longer (7 vs 5 days, p &lt; 0.05), and associated with higher expenses ($214,612 vs $ 134,195, p &lt; 0.05). In addition, inpatient admissions with colitis were more towards larger academic hospitals (80% vs 67%, p = 0.01). ICPi-treated patients with genitourinary (GU) cancers were observed more with colitis among these admissions (27% vs 15%, p &lt; 0.05). Though no difference from mortalities observed, serious complications, such as acute kidney injury (AKI) (44% vs 20%, p &lt; 0.05) and non-septic shock rates were higher (7% vs 2%, p = 0.01) among colitis admissions. Conclusions: This real-world data analysis of inpatient admissions from ICPi-treated cancer patients demonstrated colitis with diarrhea as a common safety concern over ICPi-therapies, a higher risk among patients of GU primaries, higher risk with serious medical complications: acute renal dysfunction and non-septic shock, led to increased length of stays (LOS) and financial burden. Special attention and further study may be placed among ICPi-treated GU cancer patients. [Table: see text]
The Impact of Insulin Resistance on Loss of Lung Function and Response to Treatment in Asthma
Authors: Michael C. Peters, Mark L. Schiebler, Juan Carlos Cardet, Mats W. Johansson, Ronald Sorkness, Mark D. DeBoer, Eugene R. Bleecker, Deborah A. Meyers, Mario Castro, Kaharu Sumino, Serpil C. Erzurum, Matthew C. Tattersall, Joe G. Zein, Annette T. Hastie, Wendy Moore, Bruce D. Levy, Elliot Israel, Melody G. Duvall, Brenda R. Phillips, David T. Mauger, Sally E. Wenzel, Merritt L. Fajt, Suneil K. Koliwad, Loren C. Denlinger, Prescott G. Woodruff, Nizar N. Jarjour, John V. Fahy, Michael C. Peters, Mark Schiebler, Juan Carlos Cardet, Mats W. Johansson, Ronald Sorkness, Mark D. DeBoer, Eugene R. Bleecker, Deborah A. Meyers, Mario Castro, Kaharu Sumino, Serpil C. Erzurum, Matthew C. Tattersall, Joe G. Zein, Annette T. Hastie, Wendy Moore, Bruce D. Levy, Elliot Israel, Melody Duvall, Brenda R. Phillips, David T. Mauger, Sally E. Wenzel, Merritt L. Fajt, Loren C. Denlinger, Prescott G. Woodruff, Nizar N. Jarjour, John V. Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain.
Clinicopathologic characteristics and patient outcomes of malignant phyllodes tumors: A multi-institution experience.
Authors: Aydah Al-Awadhi, Mawada Hussein, Khaled H Al Qawasmeh, Diaeddine Ahmad Trad, Jawaher Ansari, Emad Anwar, Nouri Bennini, Fathi Azribi
Journal: Journal of Clinical Oncology (2022)

e23528 Background: Phyllodes tumors (PT) are rare fibroepithelial neoplasm that start in the connective tissue of the breast. PTs are classified by their histologic features into benign, borderline, and malignant. Malignant PTs account for about 1 in 4 PTs and are most likely to come back after treatment and metastasize. This study was conducted to investigate the incidence, clinical presentation, pathological characteristics, treatment and outcome of malignant PTs in the Abu Dhabi Health Services Company (SEHA) institutions in the United Arab Emirates. This will provide a better insight on factors that influences outcome in these patients. Methods: We retrospectively analyzed data of malignant PT treated at Tawam Hospital, Sheikh Khalifa Medical City and Sheikh Shakbout Medical City between 2000 and 2020. Information was obtained from the SEHA Cancer Registry and analyzed using excel software. Results: A total of 36 patients with malignant PT were identified. All were females. The median age at diagnosis was 38 (17-60). Median BMI at diagnosis was 27 (21-47). Out of the 36 patients, 3 were diagnosed during pregnancy, 16 (44%) had a history of fibroadenoma and 8 had a family history of first degree relative with breast cancer. Initial symptom at presentation was breast mass in 30 patients and fungating breast mass in 6 patients. Out of the 26 patients, 4 (11%) had tumor &lt; 5 cm, 10 (28%) had tumor ≥5 cm and &lt; 10 cm, 22 (61%) had tumor ≥10 cm, 2 patients had heterogenous tumor with component of invasive ductal carcinoma, no patient had metastatic ipsilateral axillary adenopathy at diagnosis and 5 (14%) presented with de-novo metastatic disease (4 in the lung and 1 in the contralateral breast as the first metastatic site). Of the 31 patients with non-metastatic disease at presentation, 17 underwent mastectomy, 14 underwent lumpectomy, 14 had axillary lymph node dissection, 8 had no axillary surgery, 9 had sentinel lymph node biopsy, 16 had adjuvant radiation therapy and 2 had adjuvant chemotherapy. Of the 31 patients, 13 patients developed locoregional recurrence of which 9 had positive margin on initial surgery and 4 had negative closet margin of ≤1 cm, 7 patients developed metastatic disease of which lung and/or the chest are the main sites. Of the total population to date, 7 patients passed away from the disease. Conclusions: Malignant PT patients are a unique population with limited characterization to date. Our study demonstrates the clinical and pathological characteristics and the treatment pattern of these patients. Further analysis is underway to assess risks associated with surgical and survival outcome of this disease.
Mitochondria-targeted hydrogen sulfide donors versus acute oxidative gastric mucosal injury
Authors: Katarzyna Magierowska, Edyta Korbut, Dagmara Wójcik-Grzybek, Dominik Bakalarz, Zbigniew Sliwowski, Jakub Cieszkowski, Małgorzata Szetela, Roberta Torregrossa, Matthew Whiteman, Marcin Magierowski
Journal: Journal of Controlled Release (2022)

Hydrogen sulfide (H2S) as a gaseous molecule prevents gastrointestinal (GI)-tract against various injuries. This study aimed to evaluate for the first time the detailed molecular mechanism of mitochondria-targeting H2S-prodrugs, AP39 and RT01 in gastroprotection against ischemia/reperfusion (I/R)-induced lesions. Wistar rats exposed to I/R were pretreated i.g. with vehicle, AP39 (0.004–2 mg/kg), RT01 (0.1 mg/kg), or with AP219 (0.1 mg/kg) as structural control without ability to release H2S. AP39 was also administered with mTOR1 inhibitor, rapamycin (1 mg/kg i.g.). Gastric damage area was assessed micro−/macroscopically, gastric blood flow (GBF) by laser flowmetry, mRNA level of HIF-1α, GPx, SOD1, SOD2, annexin-A1, SOCS3, IL-1RA, IL-1β, IL-1R1, IL-1R2, TNFR2, iNOS by real-time PCR. Gastric mucosal and/or serum content of IL-1β, IL-4, IL-5, IL-10, G-CSF, M-CSF, VEGFA, GRO, RANTES, MIP-1α, MCP1, TNF-α, TIMP1, FABP3, GST-α, STAT3/5 and phosphorylation of mTOR, NF-κB, ERK, Akt was evaluated by microbeads-fluorescent assay. Mitochondrial complexes activities were measured biochemically. RNA damage was assessed as 8-OHG by ELISA. AP39 and RT01 reduced micro−/macroscopic gastric I/R-injury increasing GBF. AP39-gastroprotection was accompanied by maintained activity of mitochondrial complexes, prevented RNA oxidation and enhanced mRNA/protein expression of SOCS3, IL-1RA, annexin-A1, GST-α, HIF-1α. Rapamycin reversed AP-39-gastroprotection. AP39-gastroprotection was followed by decreased NF-κB, ERK, IL-1β and enhanced Akt and mTOR proteins phosphorylation. AP39-prevented gastric mucosal damage caused by I/R-injury, partly by mitochondrial complex activity maintenance. AP39-mediated attenuation of gastric mucosal oxidation, hypoxia and inflammation involved mTOR1 and Akt pathways activity and modulation of HIF-1α, GST-α, SOCS3, IL1RA and TIMP1 molecular interplay.
Radiomic-based model for prediction of clinically significant prostate cancer in patients with a PI-RADS 3 MRI lesion
Authors: T.A. Nguyen, F. Tixier, V. Tissot, A. Fourcade, K. Saout, A. Zambon, C. Payrard, C. Deruelle, V. Joulin, L. Doucet, D. Visvikis, G. Fournier, A. Valeri
Journal: European Urology (2022)
Bulbospongiosus muscle-sparing male sling implantation for postprostatectomy incontinence: Evaluation of safety and efficacy outcomes
Authors: E. Sacco, R. Bientinesi, C. Gandi, F. Marino, F. Gavi, S. Moretto, A. Totaro, M. Racioppi, P. Bassi
Journal: European Urology (2022)
Genomic determinants and clinical relevance of cancer-associated thrombosis in biliary tract cancers.
Authors: Federico Nichetti, Leonardo Provenzano, Daniela Miliziano, Caterina Sposetti, Chiara Pircher, Marta Bini, Andrea Franza, Giacomo Massa, Monica Niger, Maria Di Bartolomeo, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2022)

e16179 Background: Biliary tract cancers (BTCs) are a group of rare tumors with a dismal prognosis and a complex molecular landscape. In this setting, the incidence and clinical relevance of cancer-associated thrombosis (CAT) is unknown, thus BTCs are not included in common thrombotic risk scores (e.g. Khorana Score). Moreover, retrospective studies highlighted associations between thromboembolic events and some genetic alterations, such as KRAS in lung and colorectal cancer, ALK/ROS1 in lung cancer and IDH1 mutations in glioma. Nevertheless, the impact of different genomic alterations on CAT risk in BTCs patients has never been investigated. The aim of this study was to investigate for the first time the incidence and the clinical relevance of CAT in a cohort of BTC patients. In addition, we investigated the association between tumor genomics and CAT in this patients’ population. Methods: Clinical and genomic data of consecutive BTC patients who underwent extensive molecular profiling with the FoundationOneCDx panel at Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy, were collected. The association between genomic alterations and CAT incidence was investigated with the Fisher exact test, considering alterations occurring in at least 5% of patients. Cox regression was used to analyze the impact of CAT, considered as a time-dependent covariate, on overall survival (OS). Results: 140 patients were included in the analysis, mostly represented by cases of intrahepatic cholangiocarcinoma (77%). CAT occurred in 18 (13%) patients, the majority being pulmonary embolism (28%) and visceral thrombosis (44%). Pathogenic KRAS and BRCA1 mutations were found in 33% and 11% of patients with CAT, resulting significantly associated with an increased risk of thrombosis ( p = 0.041 for both). Patients who experienced CAT showed a significantly poorer OS (HR 3.29, p = &lt; 0.001). Conclusions: This is the first report describing a non-negligible incidence and significant prognostic impact of CAT in BTC patients. Future studies investigating the clinical and molecular risk factors for CAT in this population are needed to tailor thromboprophylaxis in this rare population.
Analysis of demographic and staging characteristics in patients with colorectal cancer using the SEER registry.
Authors: Monika Devanaboyina, Morgan Marie Bailey, Navkirat Kahlon, Danae M. Hamouda
Journal: Journal of Clinical Oncology (2022)

e15589 Background: Screening for colorectal cancer (CRC) has traditionally begun at age 50, with more recent guidelines suggesting beginning at age 45 to enhance earlier detection. Methods: Incidence data of CRC from the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program 21 registry was utilized for this study. This study analyzed data from 2014-2018 with 95% confidence intervals for ages 50-64, 64-74, and 75+. Localized, regional and distant metastasis were coded according to the SEER database. Results: The incidence of CRC increased with age as individuals ages 75+ had the highest incidence at 211.8 per 100,000, compared to 70.7 for ages 50-64. In the age group of 75+, the incidence of localized CRC was 70.1 (95% CI: 69.2-71.0) and regional CRC was 69.2 (68.4-70.1) which was not statistically significant. Upon analyzing sex in CRC, female patients have a statistically lower chance of presenting with CRC at 59.5, 107.6, 192.1 for the age groups 50-64, 65-74, and 75+ respectively, whereas male counterparts have rates of 82.7, 152.9, and 240.2. Analysis of Asian females showed no difference in incidence of local and regional disease for ages 50-74. For ages 75+, the incidence of regional disease at 54.6 (51.3-58.1) was much higher than local disease at 45.3 (42.3- 48.5). Of note, Asian females aged 50-64, Hispanic females ages 65 and older, and Black and White females ages 75+ were equally likely to present with local or regional disease. White males had statistically significant higher odds of localized compared to regional cancer in all age groups. Further analysis shows that Asian males have an equal incidence of local and regional disease for ages 65 and above. Black males ages 75+ and Hispanic males ages 50+ had a similar incidence of local and regional CRC. Conclusions: Ensuring equitable access to screening and earlier screening may be beneficial and improve cancer-related mortality in certain demographics. A more modern data set should be analyzed to support these findings. This analysis was limited to incidence of CRC, and future studies assessing presentation at diagnosis could be insightful.[Table: see text]
Heterogeneity in treatment regimens for AYA bone sarcomas: A comparison of outcomes at a single sarcoma center.
Authors: Andrea P. Espejo-Freire, Leticia Campoverde, Yana Kropotova, Kurt Statz-Geary, Philippos Apolinario Costa, Priscila Barreto Coelho, Steven Bialick, Gina Z. D'Amato, Emily Jonczak, Jonathan C. Trent, Aditi Dhir
Journal: Journal of Clinical Oncology (2022)

e23508 Background: Bone sarcomas account for about 5% of cancers in adolescents and young adults (AYA). Outcomes in this population are consistently inferior than children. It is poorly understood whether this is related to the tumor biology or the therapeutic approach. In addition, regimens used in AYAs are heterogeneous due to poor tolerance of pediatric regimens and lack of clinical trials specific to this population. We sought to study the therapeutic regimes and outcomes of AYA bone sarcoma patients (pts) to understand the optimal therapeutic approach better. Methods: From our institutional database, we extracted data of pts with the diagnosis of “osteosarcoma” (OS) and “Ewing sarcoma” (ES) in the AYA (15-39 yo) population from 2011-21. We included only pts with efficacy documented to different regimens. Descriptive statistics were used for patient demographics, presentation, regimens, and outcomes (Table). Objective response rate (ORR) was defined as the number of patients achieving a partial or complete response. Relapse rate (RR) was calculated for the pts that progressed after undergoing definitive curative intent treatment. Survival comparison between groups was made using the Kaplan Meier method and Log Rank Test. We used Fisher's exact test to compare differences in ORR between treatment groups. Results: We identified 30 ES and 44 OS pts. For both ES and OS, Kaplan Meier survival analysis showed no difference in presentation adjusted overall survival between treatment groups; ( x 2 .351, p .55) for ES and ( x 2 1.94 p .378) for OS. Importantly, in OS, ORR difference between Adria/IVCis and Adria/IACis was statistically significant ( p .0188). Conclusions: Our study shows the heterogeneity in first-line treatment strategies for AYA pts with bone sarcomas. For ES, response rates for VAC/IE and VAI were similar. In the OS cohort, we found ORR for Adria/IACis was 81% which was statistically different to pts receiving Adria/IVCis (ORR 30%). However, we saw relapses in 43% of pts treated with Adria/IACis. This indicates that the intra-arterial approach could be helpful for limb preservation but suggests the need for intense adjuvant chemotherapy to prevent relapses. There were no statistically significant differences in the survival outcomes of AYA bone sarcoma pts treated with pediatric versus adult regimens.[Table: see text]
Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history
Authors: Enrico Lavezzo, Monia Pacenti, Laura Manuto, Caterina Boldrin, Margherita Cattai, Marco Grazioli, Federico Bianca, Margherita Sartori, Federico Caldart, Gioele Castelli, Michele Nicoletti, Eleonora Nieddu, Elisa Salvadoretti, Beatrice Labella, Ludovico Fava, Maria Cristina Vanuzzo, Vittoria Lisi, Maria Antonello, Carmela Ileana Grimaldi, Chiara Zulian, Claudia Del Vecchio, Mario Plebani, Andrea Padoan, Daniela Maria Cirillo, Alessandra R. Brazzale, Giovanni Tonon, Stefano Toppo, Ilaria Dorigatti, Andrea Crisanti
Journal: Genome Medicine (2022)

The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects.
A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in patients with platinum-sensitive, recurrent ovarian cancer previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial.
Authors: Jung-Yun Lee, Junsik Park, Jae Kwan Lee, Dae Hoon Jeong, Se Ik Kim, Min Chul Choi, Byoung-Gie Kim, Myong Cheol Lim, Jeong-Yeol Park
Journal: Journal of Clinical Oncology (2022)

TPS5610 Background: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi. Methods: The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate and 4 of planned 44 patients have been enrolled. Clinical trial information: NCT04734665.
Impact of stringent non-pharmaceutical interventions applied during the second and third COVID-19 epidemic waves in Portugal, 9 November 2020 to 10 February 2021: an ecological study
Authors: Ana Rita Torres, Ana Paula Rodrigues, Mafalda Sousa-Uva, Irina Kislaya, Susana Silva, Liliana Antunes, Carlos Dias, Baltazar Nunes
Journal: Eurosurveillance (2022)

BackgroundNon-pharmaceutical interventions (NPIs) were implemented worldwide to control the spread of SARS-CoV-2.AimTo evaluate the impact of tiered NPIs and a nationwide lockdown on reduction of COVID-19 incidence during the second and third epidemic waves in Portugal.MethodsSurveillance data on laboratory-confirmed COVID-19 cases were used to conduct an interrupted time series analysis to estimate changes in daily incidence during a second wave tiered NPI period (9 November-18 December 2020), and a third wave lockdown period without (15-21 January 2021) and with school closure (22 January-10 February 2021).ResultsSignificant changes in trends were observed for the overall incidence rate; declining trends were observed for tiered NPIs (-1.9% per day; incidence rate ratio (IRR): 0.981; 95% confidence interval (CI): 0.973-0.989) and a lockdown period without (-3.4% per day; IRR: 0.966; 95% CI: 0.935-0.998) and with school closure (-10.3% per day, IRR: 0.897; 95% CI: 0.846-0.951). Absolute effects associated with tiered NPIs and a lockdown on a subsequent 14-day period yielded 137 cases and 437 cases per 100,000 population potentially averted, respectively.ConclusionOur results indicate that tiered NPIs implemented during the second wave caused a decline in COVID-19 incidence, although modest. Moreover, a third wave lockdown without school closure was effective in reducing COVID-19 incidence, but the addition of school closure provided the strongest effect. These findings emphasise the importance of early and assertive decision-making to control the pandemic.